Blood-brain barrier (BBB) permeability to macromolecules was assessed during seizures induced by pentylenetetrazole, bicuculline, methoxypyridoxine, methionine sulfoximine, and kainic acid. It was observed that each convulsant induced a specific pattern of regional BBB opening. This was, however, only the case when systemic blood pressure (BP) rose with seizure onset. The analysis of regional cerebral blood flow revealed that a high increase in flow in rabbits with BP rise is related to the normal flow at rest in the single brain region, but not to BBB permeability. In rabbits without BP increase, regional flow increase was low but well modulated and is possibly a better indicator for neuronal activity. The ultrastructural analysis showed that macromolecular transport over the cerebrovascular endothelium is by pinocytosis, a neurotransmitter controlled process. It is suggested that seizure-induced regional BBB opening is determined by two factors: release of neurotransmitters due to the process of autoregulation during peripheral pressure increase, and change in local neurotransmitter milieu due to the action of the convulsant and/or the seizure activity. The project is completed.